Guanylate Cyclase

Guanylatecyclase (guanylylcyclase, GC) is a lyase enzyme. Guanylylcyclase is often part of the G protein signaling cascade that is activated by low intracellular calcium levels and inhibited by high intracellular calcium levels. In response to calcium levels, guanylylcyclase synthesizes cGMP from GTP. cGMP keeps cGMP-gated channels open, allowing for the entry of calcium into the cell. The guanylylcyclase activity is modulated by the calcium-binding guanylylcyclase activating proteins (GCAP1 and GCAP2). A key mechanism by which Ca2+ modulates phototransduction in rods involves the synthesis of cGMP by guanylylcyclase (GC), regulated by a pair of Ca2+-binding GuanylylCyclase Activating Proteins (GCAP1 and GCAP2).

The second messenger cyclic guanosine monophosphate (cGMP) is generated by the heterodimeric α/β-heme protein soluble guanylatecyclase (sGC) upon activation by its endogenous ligand nitric oxide (NO). NO binds to the reduced prosthetic heme group bound to the β subunit. cGMP is a key mediator of the cardiovascular system and its effects lead to vasodilation, inhibition of smooth muscle proliferation, blockade of leukocyte infiltration and inhibition of platelet aggregation. Impairment of the cytoprotective NO/sGC/cGMP-signalling pathway is associated with the development of serious cardiovascular diseases such as hypertension or heart failure.